ES2276282T3 - Inhibidor de pten o un nuevo abridor de canales maxi-k. - Google Patents

Inhibidor de pten o un nuevo abridor de canales maxi-k. Download PDF

Info

Publication number: ES2276282T3
Authority: ES; Spain
Prior art keywords: compound; maxi; salt; carbostiryl; preparation
Prior art date: 2003-02-25
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.): Expired - Lifetime

Application number

ES04713984T

Other languages

English (en)

Spanish (es)

Inventor

Ki Whan Hong

Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)

Otsuka Pharmaceutical Co Ltd

Original Assignee

Otsuka Pharmaceutical Co Ltd

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

2003-02-25

Filing date

2004-02-24

Publication date

2007-06-16

2004-02-24 Application filed by Otsuka Pharmaceutical Co Ltd filed Critical Otsuka Pharmaceutical Co Ltd

2007-06-16 Application granted granted Critical

2007-06-16 Publication of ES2276282T3 publication Critical patent/ES2276282T3/es

2024-02-24 Anticipated expiration legal-status Critical

Status Expired - Lifetime legal-status Critical Current

Links

102000016469 Large-Conductance Calcium-Activated Potassium Channels Human genes 0.000 title description 9
108010092555 Large-Conductance Calcium-Activated Potassium Channels Proteins 0.000 title description 9
229940123940 PTEN inhibitor Drugs 0.000 title description 6
150000001875 compounds Chemical class 0.000 claims abstract description 37
238000002360 preparation method Methods 0.000 claims abstract description 28
102000014160 PTEN Phosphohydrolase Human genes 0.000 claims abstract description 21
108010011536 PTEN Phosphohydrolase Proteins 0.000 claims abstract description 21
150000003839 salts Chemical class 0.000 claims abstract description 18
239000003814 drug Substances 0.000 claims abstract description 17
125000002947 alkylene group Chemical group 0.000 claims abstract description 6
125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 5
-1 1-Cyclohexyl-1H-tetrazol-5-yl Chemical group 0.000 claims description 16
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 12
201000010099 disease Diseases 0.000 claims description 11
125000004106 butoxy group Chemical group [*]OC([H])([H])C([H])([H])C(C([H])([H])[H])([H])[H] 0.000 claims description 10
229940079593 drug Drugs 0.000 claims description 7
230000001537 neural effect Effects 0.000 claims description 7
208000019695 Migraine disease Diseases 0.000 claims description 4
206010015037 epilepsy Diseases 0.000 claims description 4
230000000926 neurological effect Effects 0.000 claims description 4
208000019901 Anxiety disease Diseases 0.000 claims description 3
206010048962 Brain oedema Diseases 0.000 claims description 3
206010052402 Gastrointestinal hypermotility Diseases 0.000 claims description 3
208000002193 Pain Diseases 0.000 claims description 3
208000018737 Parkinson disease Diseases 0.000 claims description 3
206010046543 Urinary incontinence Diseases 0.000 claims description 3
230000036506 anxiety Effects 0.000 claims description 3
208000006752 brain edema Diseases 0.000 claims description 3
208000010877 cognitive disease Diseases 0.000 claims description 2
208000018936 intestinal hypermotility Diseases 0.000 claims description 2
230000037036 intestinal hypermotility Effects 0.000 claims description 2
206010027599 migraine Diseases 0.000 claims description 2
206010010904 Convulsion Diseases 0.000 claims 1
230000006931 brain damage Effects 0.000 claims 1
231100000874 brain damage Toxicity 0.000 claims 1
208000029028 brain injury Diseases 0.000 claims 1
230000036461 convulsion Effects 0.000 claims 1
230000000472 traumatic effect Effects 0.000 claims 1
RRGUKTPIGVIEKM-UHFFFAOYSA-N cilostazol Chemical compound C=1C=C2NC(=O)CCC2=CC=1OCCCCC1=NN=NN1C1CCCCC1 RRGUKTPIGVIEKM-UHFFFAOYSA-N 0.000 description 30
229960004588 cilostazol Drugs 0.000 description 30
108091006146 Channels Proteins 0.000 description 25
230000000694 effects Effects 0.000 description 23
210000004027 cell Anatomy 0.000 description 21
241000699670 Mus sp. Species 0.000 description 20
241000699666 Mus <mouse, genus> Species 0.000 description 13
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 13
238000002474 experimental method Methods 0.000 description 12
238000000034 method Methods 0.000 description 11
229960004580 glibenclamide Drugs 0.000 description 8
ZNNLBTZKUZBEKO-UHFFFAOYSA-N glyburide Chemical compound COC1=CC=C(Cl)C=C1C(=O)NCCC1=CC=C(S(=O)(=O)NC(=O)NC2CCCCC2)C=C1 ZNNLBTZKUZBEKO-UHFFFAOYSA-N 0.000 description 8
108010068927 iberiotoxin Proteins 0.000 description 8
VDNVVLOBNHIMQA-UHFFFAOYSA-N iberiotoxin Chemical compound C1SSCC(C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(O)=O)NC(=O)C(CCCNC(N)=N)NC(=O)C1NC(=O)C(CCCCN)NC(=O)C(CCCCN)NC(=O)CNC(=O)C(CCSC)NC(=O)C(NC(=O)C(CCCCN)NC(=O)CNC(=O)C(CCCNC(N)=N)NC(=O)C(CC(O)=O)NC(=O)C(C(C)C)NC(=O)CNC(=O)C(CC=1C=CC=CC=1)NC(=O)C(CC(C)C)NC(=O)C(CC(O)=O)NC(=O)C(CCCCN)NC1=O)CSSCC1NC(=O)C(C(C)C)NC(=O)C(CO)NC(=O)C(CC=1C2=CC=CC=C2NC=1)NC(=O)C(NC(=O)C(CCC(O)=O)NC(=O)C(CCCCN)NC(=O)C(CO)NC(=O)C(C(C)C)NC(=O)C(CO)NC1=O)CSSCC1NC(=O)C(CC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(O)=O)NC(=O)C(C(C)O)NC(=O)C(NC(=O)C1NC(=O)CC1)CC1=CC=CC=C1 VDNVVLOBNHIMQA-UHFFFAOYSA-N 0.000 description 8
239000007788 liquid Substances 0.000 description 8
238000012360 testing method Methods 0.000 description 7
210000004556 brain Anatomy 0.000 description 6
230000002401 inhibitory effect Effects 0.000 description 6
238000002347 injection Methods 0.000 description 6
239000007924 injection Substances 0.000 description 6
239000002609 medium Substances 0.000 description 6
239000000203 mixture Substances 0.000 description 6
230000026731 phosphorylation Effects 0.000 description 6
238000006366 phosphorylation reaction Methods 0.000 description 6
239000011780 sodium chloride Substances 0.000 description 6
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 6
OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 5
229920002134 Carboxymethyl cellulose Polymers 0.000 description 5
239000004480 active ingredient Substances 0.000 description 5
230000006399 behavior Effects 0.000 description 5
239000011575 calcium Substances 0.000 description 5
229910052791 calcium Inorganic materials 0.000 description 5
239000001768 carboxy methyl cellulose Substances 0.000 description 5
230000003834 intracellular effect Effects 0.000 description 5
208000024827 Alzheimer disease Diseases 0.000 description 4
101800001718 Amyloid-beta protein Proteins 0.000 description 4
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 4
241001465754 Metazoa Species 0.000 description 4
239000002775 capsule Substances 0.000 description 4
235000010948 carboxy methyl cellulose Nutrition 0.000 description 4
239000008112 carboxymethyl-cellulose Substances 0.000 description 4
229940105329 carboxymethylcellulose Drugs 0.000 description 4
210000002064 heart cell Anatomy 0.000 description 4
LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 4
238000007911 parenteral administration Methods 0.000 description 4
QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 4
DAEPDZWVDSPTHF-UHFFFAOYSA-M sodium pyruvate Chemical compound [Na+].CC(=O)C([O-])=O DAEPDZWVDSPTHF-UHFFFAOYSA-M 0.000 description 4
239000000243 solution Substances 0.000 description 4
230000002269 spontaneous effect Effects 0.000 description 4
229940124549 vasodilator Drugs 0.000 description 4
239000003071 vasodilator agent Substances 0.000 description 4
102000013455 Amyloid beta-Peptides Human genes 0.000 description 3
108010090849 Amyloid beta-Peptides Proteins 0.000 description 3
WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 3
206010061296 Motor dysfunction Diseases 0.000 description 3
239000002202 Polyethylene glycol Substances 0.000 description 3
DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
206010040047 Sepsis Diseases 0.000 description 3
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
208000030886 Traumatic Brain injury Diseases 0.000 description 3
238000004458 analytical method Methods 0.000 description 3
230000001773 anti-convulsant effect Effects 0.000 description 3
239000001961 anticonvulsive agent Substances 0.000 description 3
229960003965 antiepileptics Drugs 0.000 description 3
210000004369 blood Anatomy 0.000 description 3
239000008280 blood Substances 0.000 description 3
210000004958 brain cell Anatomy 0.000 description 3
230000004709 cell invasion Effects 0.000 description 3
239000003795 chemical substances by application Substances 0.000 description 3
238000007405 data analysis Methods 0.000 description 3
230000003247 decreasing effect Effects 0.000 description 3
239000012153 distilled water Substances 0.000 description 3
235000019441 ethanol Nutrition 0.000 description 3
239000012091 fetal bovine serum Substances 0.000 description 3
239000008103 glucose Substances 0.000 description 3
239000008187 granular material Substances 0.000 description 3
230000005764 inhibitory process Effects 0.000 description 3
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 3
239000012528 membrane Substances 0.000 description 3
238000002156 mixing Methods 0.000 description 3
239000008024 pharmaceutical diluent Substances 0.000 description 3
229920001223 polyethylene glycol Polymers 0.000 description 3
230000001629 suppression Effects 0.000 description 3
230000004083 survival effect Effects 0.000 description 3
238000012546 transfer Methods 0.000 description 3
230000009529 traumatic brain injury Effects 0.000 description 3
WNWHHMBRJJOGFJ-UHFFFAOYSA-N 16-methylheptadecan-1-ol Chemical compound CC(C)CCCCCCCCCCCCCCCO WNWHHMBRJJOGFJ-UHFFFAOYSA-N 0.000 description 2
JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 2
108091003079 Bovine Serum Albumin Proteins 0.000 description 2
229920002261 Corn starch Polymers 0.000 description 2
238000002965 ELISA Methods 0.000 description 2
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
239000007995 HEPES buffer Substances 0.000 description 2
229920002153 Hydroxypropyl cellulose Polymers 0.000 description 2
ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 2
229930182816 L-glutamine Natural products 0.000 description 2
GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 2
206010029260 Neuroblastoma Diseases 0.000 description 2
ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
229920001214 Polysorbate 60 Polymers 0.000 description 2
102000004257 Potassium Channel Human genes 0.000 description 2
PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 2
229930006000 Sucrose Natural products 0.000 description 2
CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 2
230000009471 action Effects 0.000 description 2
230000003178 anti-diabetic effect Effects 0.000 description 2
239000003472 antidiabetic agent Substances 0.000 description 2
239000012736 aqueous medium Substances 0.000 description 2
210000003050 axon Anatomy 0.000 description 2
239000000872 buffer Substances 0.000 description 2
238000004113 cell culture Methods 0.000 description 2
230000012292 cell migration Effects 0.000 description 2
229920002678 cellulose Polymers 0.000 description 2
239000001913 cellulose Substances 0.000 description 2
230000001149 cognitive effect Effects 0.000 description 2
239000003086 colorant Substances 0.000 description 2
238000007796 conventional method Methods 0.000 description 2
239000008120 corn starch Substances 0.000 description 2
125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 2
239000002552 dosage form Substances 0.000 description 2
239000000839 emulsion Substances 0.000 description 2
238000001914 filtration Methods 0.000 description 2
235000003599 food sweetener Nutrition 0.000 description 2
230000006870 function Effects 0.000 description 2
239000001863 hydroxypropyl cellulose Substances 0.000 description 2
235000010977 hydroxypropyl cellulose Nutrition 0.000 description 2
239000003112 inhibitor Substances 0.000 description 2
239000007951 isotonicity adjuster Substances 0.000 description 2
239000008101 lactose Substances 0.000 description 2
239000000463 material Substances 0.000 description 2
230000001404 mediated effect Effects 0.000 description 2
235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 2
239000004292 methyl p-hydroxybenzoate Substances 0.000 description 2
229960002216 methylparaben Drugs 0.000 description 2
230000001067 neuroprotector Effects 0.000 description 2
108020001213 potassium channel Proteins 0.000 description 2
239000003755 preservative agent Substances 0.000 description 2
235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 2
239000004405 propyl p-hydroxybenzoate Substances 0.000 description 2
229960003415 propylparaben Drugs 0.000 description 2
108090000623 proteins and genes Proteins 0.000 description 2
102000004169 proteins and genes Human genes 0.000 description 2
239000000523 sample Substances 0.000 description 2
230000006403 short-term memory Effects 0.000 description 2
210000004927 skin cell Anatomy 0.000 description 2
HRZFUMHJMZEROT-UHFFFAOYSA-L sodium disulfite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])(=O)=O HRZFUMHJMZEROT-UHFFFAOYSA-L 0.000 description 2
229940001584 sodium metabisulfite Drugs 0.000 description 2
235000010262 sodium metabisulphite Nutrition 0.000 description 2
229940054269 sodium pyruvate Drugs 0.000 description 2
208000010110 spontaneous platelet aggregation Diseases 0.000 description 2
239000011550 stock solution Substances 0.000 description 2
239000000758 substrate Substances 0.000 description 2
239000005720 sucrose Substances 0.000 description 2
239000000725 suspension Substances 0.000 description 2
239000003765 sweetening agent Substances 0.000 description 2
239000003826 tablet Substances 0.000 description 2
230000009261 transgenic effect Effects 0.000 description 2
210000001364 upper extremity Anatomy 0.000 description 2
239000003981 vehicle Substances 0.000 description 2
JNYAEWCLZODPBN-JGWLITMVSA-N (2r,3r,4s)-2-[(1r)-1,2-dihydroxyethyl]oxolane-3,4-diol Chemical compound OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O JNYAEWCLZODPBN-JGWLITMVSA-N 0.000 description 1
XUHRVZXFBWDCFB-QRTDKPMLSA-N (3R)-4-[[(3S,6S,9S,12R,15S,18R,21R,24R,27R,28R)-12-(3-amino-3-oxopropyl)-6-[(2S)-butan-2-yl]-3-(2-carboxyethyl)-18-(hydroxymethyl)-28-methyl-9,15,21,24-tetrakis(2-methylpropyl)-2,5,8,11,14,17,20,23,26-nonaoxo-1-oxa-4,7,10,13,16,19,22,25-octazacyclooctacos-27-yl]amino]-3-[[(2R)-2-[[(3S)-3-hydroxydecanoyl]amino]-4-methylpentanoyl]amino]-4-oxobutanoic acid Chemical compound CCCCCCC[C@H](O)CC(=O)N[C@H](CC(C)C)C(=O)N[C@H](CC(O)=O)C(=O)N[C@@H]1[C@@H](C)OC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](CCC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](CO)NC(=O)[C@@H](CC(C)C)NC(=O)[C@@H](CC(C)C)NC1=O)[C@@H](C)CC XUHRVZXFBWDCFB-QRTDKPMLSA-N 0.000 description 1
125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 description 1
BDDLHHRCDSJVKV-UHFFFAOYSA-N 7028-40-2 Chemical compound CC(O)=O.CC(O)=O.CC(O)=O.CC(O)=O BDDLHHRCDSJVKV-UHFFFAOYSA-N 0.000 description 1
244000215068 Acacia senegal Species 0.000 description 1
GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
108010039627 Aprotinin Proteins 0.000 description 1
101100297694 Arabidopsis thaliana PIP2-7 gene Proteins 0.000 description 1
108010010803 Gelatin Proteins 0.000 description 1
229920000084 Gum arabic Polymers 0.000 description 1
241000699660 Mus musculus Species 0.000 description 1
239000000020 Nitrocellulose Substances 0.000 description 1
206010030113 Oedema Diseases 0.000 description 1
101150073900 PTEN gene Proteins 0.000 description 1
102000045595 Phosphoprotein Phosphatases Human genes 0.000 description 1
108700019535 Phosphoprotein Phosphatases Proteins 0.000 description 1
102000004160 Phosphoric Monoester Hydrolases Human genes 0.000 description 1
108090000608 Phosphoric Monoester Hydrolases Proteins 0.000 description 1
239000004372 Polyvinyl alcohol Substances 0.000 description 1
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
NPYPAHLBTDXSSS-UHFFFAOYSA-N Potassium ion Chemical compound [K+] NPYPAHLBTDXSSS-UHFFFAOYSA-N 0.000 description 1
101100456541 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) MEC3 gene Proteins 0.000 description 1
101100483663 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) UFD1 gene Proteins 0.000 description 1
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
229920002472 Starch Polymers 0.000 description 1
238000000692 Student's t-test Methods 0.000 description 1
102100024547 Tensin-1 Human genes 0.000 description 1
108010088950 Tensins Proteins 0.000 description 1
229920004890 Triton X-100 Polymers 0.000 description 1
239000013504 Triton X-100 Substances 0.000 description 1
102000044209 Tumor Suppressor Genes Human genes 0.000 description 1
108700025716 Tumor Suppressor Genes Proteins 0.000 description 1
239000000205 acacia gum Substances 0.000 description 1
235000010489 acacia gum Nutrition 0.000 description 1
DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 1
230000003444 anaesthetic effect Effects 0.000 description 1
230000000702 anti-platelet effect Effects 0.000 description 1
239000003146 anticoagulant agent Substances 0.000 description 1
229960004405 aprotinin Drugs 0.000 description 1
239000007864 aqueous solution Substances 0.000 description 1
239000008135 aqueous vehicle Substances 0.000 description 1
238000003556 assay Methods 0.000 description 1
WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
230000015572 biosynthetic process Effects 0.000 description 1
230000037396 body weight Effects 0.000 description 1
238000004364 calculation method Methods 0.000 description 1
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
230000005754 cellular signaling Effects 0.000 description 1
238000005119 centrifugation Methods 0.000 description 1
206010008118 cerebral infarction Diseases 0.000 description 1
208000026106 cerebrovascular disease Diseases 0.000 description 1
239000003153 chemical reaction reagent Substances 0.000 description 1
210000000349 chromosome Anatomy 0.000 description 1
238000004140 cleaning Methods 0.000 description 1
239000011538 cleaning material Substances 0.000 description 1
230000001010 compromised effect Effects 0.000 description 1
239000012059 conventional drug carrier Substances 0.000 description 1
125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
125000000640 cyclooctyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
230000001419 dependent effect Effects 0.000 description 1
239000000645 desinfectant Substances 0.000 description 1
235000014113 dietary fatty acids Nutrition 0.000 description 1
LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 1
208000035475 disorder Diseases 0.000 description 1
238000004090 dissolution Methods 0.000 description 1
239000003937 drug carrier Substances 0.000 description 1
238000005516 engineering process Methods 0.000 description 1
150000002148 esters Chemical class 0.000 description 1
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
DEFVIWRASFVYLL-UHFFFAOYSA-N ethylene glycol bis(2-aminoethyl)tetraacetic acid Chemical compound OC(=O)CN(CC(O)=O)CCOCCOCCN(CC(O)=O)CC(O)=O DEFVIWRASFVYLL-UHFFFAOYSA-N 0.000 description 1
238000000605 extraction Methods 0.000 description 1
239000000194 fatty acid Substances 0.000 description 1
229930195729 fatty acid Natural products 0.000 description 1
150000004665 fatty acids Chemical class 0.000 description 1
210000003608 fece Anatomy 0.000 description 1
239000000796 flavoring agent Substances 0.000 description 1
235000013305 food Nutrition 0.000 description 1
235000013355 food flavoring agent Nutrition 0.000 description 1
239000003205 fragrance Substances 0.000 description 1
238000004108 freeze drying Methods 0.000 description 1
238000007710 freezing Methods 0.000 description 1
230000008014 freezing Effects 0.000 description 1
230000000855 fungicidal effect Effects 0.000 description 1
239000000417 fungicide Substances 0.000 description 1
239000000499 gel Substances 0.000 description 1
229920000159 gelatin Polymers 0.000 description 1
239000008273 gelatin Substances 0.000 description 1
239000007903 gelatin capsule Substances 0.000 description 1
235000019322 gelatine Nutrition 0.000 description 1
235000011852 gelatine desserts Nutrition 0.000 description 1
239000003193 general anesthetic agent Substances 0.000 description 1
239000011521 glass Substances 0.000 description 1
235000011187 glycerol Nutrition 0.000 description 1
230000002102 hyperpolarization Effects 0.000 description 1
230000006872 improvement Effects 0.000 description 1
ZPNFWUPYTFPOJU-LPYSRVMUSA-N iniprol Chemical compound C([C@H]1C(=O)NCC(=O)NCC(=O)N[C@H]2CSSC[C@H]3C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@H](C(N[C@H](C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=4C=CC(O)=CC=4)C(=O)N[C@@H](CC=4C=CC=CC=4)C(=O)N[C@@H](CC=4C=CC(O)=CC=4)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC=4C=CC=CC=4)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(N)=N)NC2=O)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](CC=2C=CC=CC=2)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H]2N(CCC2)C(=O)[C@@H](N)CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N2[C@@H](CCC2)C(=O)N2[C@@H](CCC2)C(=O)N[C@@H](CC=2C=CC(O)=CC=2)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N2[C@@H](CCC2)C(=O)N3)C(=O)NCC(=O)NCC(=O)N[C@@H](C)C(O)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@H](C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@H](C(=O)N1)C(C)C)[C@@H](C)O)[C@@H](C)CC)=O)[C@@H](C)CC)C1=CC=C(O)C=C1 ZPNFWUPYTFPOJU-LPYSRVMUSA-N 0.000 description 1
150000002632 lipids Chemical class 0.000 description 1
239000000314 lubricant Substances 0.000 description 1
239000012139 lysis buffer Substances 0.000 description 1
235000019359 magnesium stearate Nutrition 0.000 description 1
239000003550 marker Substances 0.000 description 1
238000002483 medication Methods 0.000 description 1
230000028161 membrane depolarization Effects 0.000 description 1
229920000609 methyl cellulose Polymers 0.000 description 1
239000001923 methylcellulose Substances 0.000 description 1
235000010981 methylcellulose Nutrition 0.000 description 1
230000005012 migration Effects 0.000 description 1
238000013508 migration Methods 0.000 description 1
239000004570 mortar (masonry) Substances 0.000 description 1
210000002569 neuron Anatomy 0.000 description 1
230000004112 neuroprotection Effects 0.000 description 1
229920001220 nitrocellulos Polymers 0.000 description 1
231100000252 nontoxic Toxicity 0.000 description 1
230000003000 nontoxic effect Effects 0.000 description 1
239000003960 organic solvent Substances 0.000 description 1
239000008023 pharmaceutical filler Substances 0.000 description 1
239000000825 pharmaceutical preparation Substances 0.000 description 1
230000000144 pharmacologic effect Effects 0.000 description 1
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
WVDDGKGOMKODPV-ZQBYOMGUSA-N phenyl(114C)methanol Chemical compound O[14CH2]C1=CC=CC=C1 WVDDGKGOMKODPV-ZQBYOMGUSA-N 0.000 description 1
239000002953 phosphate buffered saline Substances 0.000 description 1
230000035790 physiological processes and functions Effects 0.000 description 1
229920002451 polyvinyl alcohol Polymers 0.000 description 1
235000019422 polyvinyl alcohol Nutrition 0.000 description 1
229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
239000001267 polyvinylpyrrolidone Substances 0.000 description 1
235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
239000011591 potassium Substances 0.000 description 1
229910052700 potassium Inorganic materials 0.000 description 1
229910001414 potassium ion Inorganic materials 0.000 description 1
230000003389 potentiating effect Effects 0.000 description 1
239000000843 powder Substances 0.000 description 1
230000002265 prevention Effects 0.000 description 1
125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
230000008569 process Effects 0.000 description 1
235000013772 propylene glycol Nutrition 0.000 description 1
230000009467 reduction Effects 0.000 description 1
230000000284 resting effect Effects 0.000 description 1
238000007789 sealing Methods 0.000 description 1
210000003491 skin Anatomy 0.000 description 1
210000002460 smooth muscle Anatomy 0.000 description 1
235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
239000007901 soft capsule Substances 0.000 description 1
239000002904 solvent Substances 0.000 description 1
239000003381 stabilizer Substances 0.000 description 1
235000019698 starch Nutrition 0.000 description 1
238000007619 statistical method Methods 0.000 description 1
230000004936 stimulating effect Effects 0.000 description 1
230000000638 stimulation Effects 0.000 description 1
238000003756 stirring Methods 0.000 description 1
239000000126 substance Substances 0.000 description 1
125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 1
239000000829 suppository Substances 0.000 description 1
235000020357 syrup Nutrition 0.000 description 1
239000006188 syrup Substances 0.000 description 1
239000000454 talc Substances 0.000 description 1
235000012222 talc Nutrition 0.000 description 1
229910052623 talc Inorganic materials 0.000 description 1
125000000383 tetramethylene group Chemical group [H]C([H])([*:1])C([H])([H])C([H])([H])C([H])([H])[*:2] 0.000 description 1
RTKIYNMVFMVABJ-UHFFFAOYSA-L thimerosal Chemical compound [Na+].CC[Hg]SC1=CC=CC=C1C([O-])=O RTKIYNMVFMVABJ-UHFFFAOYSA-L 0.000 description 1
229940033663 thimerosal Drugs 0.000 description 1
210000001519 tissue Anatomy 0.000 description 1
230000000699 topical effect Effects 0.000 description 1
238000011830 transgenic mouse model Methods 0.000 description 1
230000001052 transient effect Effects 0.000 description 1
239000001226 triphosphate Substances 0.000 description 1
235000011178 triphosphate Nutrition 0.000 description 1
230000003442 weekly effect Effects 0.000 description 1
238000005303 weighing Methods 0.000 description 1

Classifications

- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
- A61K31/4709—Non-condensed quinolines and containing further heterocyclic rings
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/06—Anti-spasmodics, e.g. drugs for colics, esophagic dyskinesia
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/06—Anti-spasmodics
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A61P15/04—Drugs for genital or sexual disorders; Contraceptives for inducing labour or abortion; Uterotonics
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A61P15/06—Antiabortive agents; Labour repressants
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/02—Drugs for disorders of the nervous system for peripheral neuropathies
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/04—Centrally acting analgesics, e.g. opioids
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/06—Antimigraine agents
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/08—Antiepileptics; Anticonvulsants
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/22—Anxiolytics
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/24—Antidepressants
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/10—Antioedematous agents; Diuretics

Landscapes

Health & Medical Sciences (AREA)
Animal Behavior & Ethology (AREA)
Chemical & Material Sciences (AREA)
Veterinary Medicine (AREA)
Public Health (AREA)
Medicinal Chemistry (AREA)
General Health & Medical Sciences (AREA)
Pharmacology & Pharmacy (AREA)
Life Sciences & Earth Sciences (AREA)
Bioinformatics & Cheminformatics (AREA)
Engineering & Computer Science (AREA)
Organic Chemistry (AREA)
General Chemical & Material Sciences (AREA)
Chemical Kinetics & Catalysis (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Neurosurgery (AREA)
Biomedical Technology (AREA)
Neurology (AREA)
Pain & Pain Management (AREA)
Epidemiology (AREA)
Reproductive Health (AREA)
Endocrinology (AREA)
Pregnancy & Childbirth (AREA)
Psychiatry (AREA)
Gynecology & Obstetrics (AREA)
Urology & Nephrology (AREA)
Psychology (AREA)
Hospice & Palliative Care (AREA)
Hematology (AREA)
Diabetes (AREA)
Communicable Diseases (AREA)
Oncology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Plural Heterocyclic Compounds (AREA)

ES04713984T 2003-02-25 2004-02-24 Inhibidor de pten o un nuevo abridor de canales maxi-k. Expired - Lifetime ES2276282T3 (es)

Applications Claiming Priority (4)

Application Number	Priority Date	Filing Date
US44943503P	2003-02-25	2003-02-25
US449435P		2003-02-25
US44958903P	2003-02-26	2003-02-26
US449589P		2003-02-26

Publications (1)

Publication Number	Publication Date
ES2276282T3 true ES2276282T3 (es)	2007-06-16

Family

ID=32930512

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
ES04713984T Expired - Lifetime ES2276282T3 (es)	2003-02-25	2004-02-24	Inhibidor de pten o un nuevo abridor de canales maxi-k.

Country Status (19)

Country	Link
US (3)	US7825130B2 (de)
EP (1)	EP1599205B1 (de)
JP (3)	JP4590397B2 (de)
KR (1)	KR101031163B1 (de)
CN (2)	CN1780623B (de)
AR (1)	AR043379A1 (de)
AT (1)	ATE345800T1 (de)
AU (1)	AU2004216340B9 (de)
BR (1)	BRPI0407832A (de)
CA (1)	CA2515590C (de)
CY (1)	CY1106294T1 (de)
DE (1)	DE602004003348T2 (de)
DK (1)	DK1599205T3 (de)
ES (1)	ES2276282T3 (de)
MX (1)	MXPA05008996A (de)
MY (1)	MY136863A (de)
PT (1)	PT1599205E (de)
TW (1)	TWI323660B (de)
WO (1)	WO2004075897A1 (de)

Families Citing this family (16)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
TWI323660B (en) *	2003-02-25	2010-04-21	Otsuka Pharma Co Ltd	Pten inhibitor or maxi-k channels opener
TW200848041A (en)	2007-03-30	2008-12-16	Otsuka Pharma Co Ltd	A medicament for treating schizophrenia comprising cilostazol
MX2009012583A (es) *	2007-05-22	2010-03-08	Otsuka Pharma Co Ltd	Un medicamento que comprende un derivado de carbostirilo y donepezilo para tratar enfermedad de alzheimer.
AR067746A1 (es) *	2007-08-02	2009-10-21	Otsuka Pharma Co Ltd	Un medicamento para tratar glaucoma que comprende como elemento activo compuesto de ciclodextrina - clatrato de cilostazol
JP5560203B2 (ja)	2008-01-17	2014-07-23	クイ・リウ	卵胞のインビトロ成熟方法
AR070816A1 (es) *	2008-03-14	2010-05-05	Otsuka Pharma Co Ltd	Farmaco de combinacion para tratar trastornos vasculares
US20110189308A1 (en) *	2008-03-17	2011-08-04	Asa Abeliovich	Methods to treat neurodegenerative conditions or diseases by targeting components of a pten signaling pathway
DK2502623T3 (en)	2008-06-06	2016-07-04	Children's Medical Center Corp	Promoting axonregeneration the adult cns by management of protein translation
CN102666845B (zh) *	2009-10-16	2015-06-10	不列颠哥伦比亚大学	磷酸酶和张力蛋白同系物(pten)抑制剂组合物,用途以及方法
EP2322163A1 (de) *	2009-11-03	2011-05-18	Pharnext	Neue therapeutische Ansätze zur Behandlung von Alzheimer-Krankheit
WO2013067125A1 (en)	2011-11-01	2013-05-10	Children's Medical Center Corporation	Co-activation of mtor and stat3 pathways to promote neuronal survival and regeneration
MX2014015310A (es) *	2012-06-15	2015-07-06	Found Biomedical Res & Innov	Agente profilactico y/o terapeutico para el deterioro cognoscitivo leve.
JP2016040542A (ja) *	2014-08-13	2016-03-24	学校法人金沢医科大学	認知症治療薬または認知症治療薬候補物質のスクリーニング方法
JP2017070404A (ja) *	2015-10-06	2017-04-13	アンディチャオ	トイレ床面の清潔な芳香パッド
US20190142820A1 (en) *	2016-05-19	2019-05-16	National Cerebral And Cardiovascular Center	Drug for preventing and/or treating dementia
EP4151213A4 (de) *	2020-05-11	2024-05-29	Shimadzu Corporation	Therapeutikum für leichte kognitive beeinträchtigung

Family Cites Families (22)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
JPS5535019A (en) *	1978-09-01	1980-03-11	Otsuka Pharmaceut Co Ltd	Carbostyryl derivative
JPS5649378A (en) *	1979-08-25	1981-05-02	Otsuka Pharmaceut Co Ltd	Tetrazolylalkoxycarbostyril derivative
JPH0653666B2 (ja)	1990-10-22	1994-07-20	大塚製薬株式会社	ヒトの糖尿病性知覚障害および末梢神経障害の治療剤
JPH0614444A (ja) *	1992-06-25	1994-01-21	Central Japan Railway Co	電力ケーブル接続部の固定装置
JPH06239745A (ja) *	1992-12-24	1994-08-30	Otsuka Pharmaceut Co Ltd	乾癬治療剤
AU5715994A (en) *	1992-12-24	1994-07-19	Otsuka Pharmaceutical Co., Ltd.	Psoriasis remedy
JPH0776584A (ja)	1993-09-07	1995-03-20	Otsuka Pharmaceut Co Ltd	内皮細胞障害抑制剤
JP3944257B2 (ja)	1995-12-07	2007-07-11	大塚製薬株式会社	肝実質細胞増殖因子産生増加剤
US6322524B1 (en) *	1997-08-28	2001-11-27	Visco Technologies, Inc.	Dual riser/single capillary viscometer
US6322525B1 (en) *	1997-08-28	2001-11-27	Visco Technologies, Inc.	Method of analyzing data from a circulating blood viscometer for determining absolute and effective blood viscosity
US6428488B1 (en) *	1997-08-28	2002-08-06	Kenneth Kensey	Dual riser/dual capillary viscometer for newtonian and non-newtonian fluids
US6019735A (en) *	1997-08-28	2000-02-01	Visco Technologies, Inc.	Viscosity measuring apparatus and method of use
US6187790B1 (en) *	1999-03-04	2001-02-13	Neal R. Cutler	Use of cilostazol for treatment of sexual dysfunction
JP2002537231A (ja) *	1998-05-01	2002-11-05	カトラー，ニール，アール	特定の患者群における性的機能障害の治療
US6267985B1 (en) *	1999-06-30	2001-07-31	Lipocine Inc.	Clear oil-containing pharmaceutical compositions
US6294192B1 (en) *	1999-02-26	2001-09-25	Lipocine, Inc.	Triglyceride-free compositions and methods for improved delivery of hydrophobic therapeutic agents
US6257985B1 (en) *	1999-10-01	2001-07-10	Rexnord Corporation	Global shaft coupling
US6484565B2 (en) *	1999-11-12	2002-11-26	Drexel University	Single riser/single capillary viscometer using mass detection or column height detection
JP4159224B2 (ja)	2000-02-29	2008-10-01	三洋電機株式会社	食器洗浄機
US6458804B1 (en) *	2001-01-26	2002-10-01	R.T. Alamo Venturesi, Llc	Methods for the treatment of central nervous system disorders in certain patient groups
US6743806B2 (en)	2002-10-23	2004-06-01	Otsuka Pharmaceutical Company, Limited	Active oxygen scavenger
TWI323660B (en) *	2003-02-25	2010-04-21	Otsuka Pharma Co Ltd	Pten inhibitor or maxi-k channels opener

2004
- 2004-02-11 TW TW093103143A patent/TWI323660B/zh not_active IP Right Cessation
- 2004-02-17 MY MYPI20040511A patent/MY136863A/en unknown
- 2004-02-24 AU AU2004216340A patent/AU2004216340B9/en not_active Ceased
- 2004-02-24 MX MXPA05008996A patent/MXPA05008996A/es active IP Right Grant
- 2004-02-24 AT AT04713984T patent/ATE345800T1/de active
- 2004-02-24 US US10/546,632 patent/US7825130B2/en not_active Expired - Fee Related
- 2004-02-24 AR ARP040100573A patent/AR043379A1/es unknown
- 2004-02-24 EP EP04713984A patent/EP1599205B1/de not_active Expired - Lifetime
- 2004-02-24 JP JP2006502683A patent/JP4590397B2/ja not_active Expired - Fee Related
- 2004-02-24 ES ES04713984T patent/ES2276282T3/es not_active Expired - Lifetime
- 2004-02-24 KR KR1020057015646A patent/KR101031163B1/ko not_active Expired - Fee Related
- 2004-02-24 DK DK04713984T patent/DK1599205T3/da active
- 2004-02-24 CN CN2004800111403A patent/CN1780623B/zh not_active Expired - Fee Related
- 2004-02-24 WO PCT/JP2004/002146 patent/WO2004075897A1/en not_active Ceased
- 2004-02-24 CA CA2515590A patent/CA2515590C/en not_active Expired - Fee Related
- 2004-02-24 BR BRPI0407832-2A patent/BRPI0407832A/pt not_active IP Right Cessation
- 2004-02-24 PT PT04713984T patent/PT1599205E/pt unknown
- 2004-02-24 DE DE602004003348T patent/DE602004003348T2/de not_active Expired - Lifetime
- 2004-02-24 CN CN201010130082.3A patent/CN101829116B/zh not_active Expired - Fee Related
2006
- 2006-12-19 CY CY20061101814T patent/CY1106294T1/el unknown
2009
- 2009-12-30 US US12/650,275 patent/US8329731B2/en not_active Expired - Fee Related
2010
- 2010-08-12 JP JP2010180661A patent/JP5208172B2/ja not_active Expired - Lifetime
2012
- 2012-11-07 US US13/671,448 patent/US8653104B2/en not_active Expired - Fee Related
2013
- 2013-01-10 JP JP2013002314A patent/JP5566482B2/ja not_active Expired - Lifetime

Also Published As

Publication number	Publication date
US20060154963A1 (en)	2006-07-13
TWI323660B (en)	2010-04-21
US7825130B2 (en)	2010-11-02
US20130065921A1 (en)	2013-03-14
EP1599205A1 (de)	2005-11-30
AU2004216340B2 (en)	2008-07-31
HK1148225A1 (zh)	2011-09-02
CA2515590C (en)	2011-09-13
CN1780623B (zh)	2011-09-14
PT1599205E (pt)	2007-01-31
CN101829116B (zh)	2015-11-25
US8653104B2 (en)	2014-02-18
AU2004216340B9 (en)	2008-09-18
DE602004003348T2 (de)	2007-05-31
JP5208172B2 (ja)	2013-06-12
CN1780623A (zh)	2006-05-31
CA2515590A1 (en)	2004-09-10
CY1106294T1 (el)	2011-10-12
BRPI0407832A (pt)	2006-02-14
KR101031163B1 (ko)	2011-04-27
US20100113515A1 (en)	2010-05-06
JP2013082735A (ja)	2013-05-09
CN101829116A (zh)	2010-09-15
ATE345800T1 (de)	2006-12-15
JP2010285456A (ja)	2010-12-24
EP1599205B1 (de)	2006-11-22
AR043379A1 (es)	2005-07-27
KR20050098960A (ko)	2005-10-12
MY136863A (en)	2008-11-28
MXPA05008996A (es)	2005-10-18
US8329731B2 (en)	2012-12-11
HK1091409A1 (en)	2007-01-19
TW200501954A (en)	2005-01-16
AU2004216340A1 (en)	2004-09-10
JP5566482B2 (ja)	2014-08-06
JP2006518732A (ja)	2006-08-17
JP4590397B2 (ja)	2010-12-01
WO2004075897A1 (en)	2004-09-10
DK1599205T3 (da)	2007-03-26
DE602004003348D1 (de)	2007-01-04

Publication	Publication Date	Title
US8653104B2 (en)	2014-02-18	PTEN inhibitor or Maxi-K channels opener
ES2460617T3 (es)	2014-05-14	Combinación de pilocarpina y tiamazol para tratar la enfermedad de Charcot-Marie-Tooth y los trastornos relacionados
ES2969532T3 (es)	2024-05-21	3-(4-((4-(Morfolinometil-bencil)oxi)-1-oxoisoindolin-2-il)piperidin-2,6-diona para el tratamiento de lupus eritematoso sistémico
US20050272722A1 (en)	2005-12-08	Methods for the treatment of synucleinopathies
Gouveia et al.	2023	Reduction of aggressive behaviour following hypothalamic deep brain stimulation: Involvement of 5-HT1A and testosterone
US7087581B1 (en)	2006-08-08	Method for the treatment of diseases or disorders of the inner ear
US10137156B2 (en)	2018-11-27	Composition comprising neural cell and elastin-like polypeptide for treating Parkinson's disease
ES2369760T3 (es)	2011-12-05	Péptido bloqueante para la secreción de células inflamatorias.
ES2952610T3 (es)	2023-11-02	Métodos para tratar o aliviar trastornos mentales y síntomas asociados
US11730769B2 (en)	2023-08-22	Compositions and methods for Williams Syndrome (WS) therapy
ES2424627T3 (es)	2013-10-07	Una composición que comprende (R)-Spiro[l-azabiciclo[2.2.2]octano-3,2'(3'H)-furo[2,3-b]piridina (AZD0328) y su uso en el tratamiento de la enfermedad de Alzheimer, ADHD o disfunción cognitiva
CN110384712B (zh)	2022-03-04	核酸适配子在制备治疗阿尔茨海默氏病药物中的应用
JP2018534287A (ja)	2018-11-22	Ｓｋチャネル阻害剤による学習障害および他の神経障害の治療
HK1091409B (en)	2011-12-23	Pten inhibitor or maxi-k channels opener
Chang et al.	2023	Using in vivo cerebellar electroporation to study neuronal cell proliferation and differentiation in a joubert syndrome mouse model
WO2016092139A1 (es)	2016-06-16	Composiciones para el tratamiento de enfermedades de las motoneuronas
Corey-Bloom et al.	2004	O1-05-01 The safety and efficacy of an extended-release formulation of galantamine (reminyl ER) in the treatment of Alzheimer's disease
Ramos	1997	The functional significance of the proto-oncogene, c-fos, in the onset and offset of estrous behavior in the female hamster: Is the AP-1 transcription factor involved?
Hartmann	2006	Adaptive responses of central cholinergic systems in transgenic mice
BR102012021840A2 (pt)	2015-06-23	Processo de obtenção, uso e aplicações farmacêuticas da formulação lipossomal convencional contendo nimodipina direcionada ao tratamento da ansiedade e depressão e convulsão